HIV

pathophysiology
Cellular activation plays an important role in the replication cycle of HIV and is critical to
the pathogenesis of HIV disease
MUCOSAL TRANSMSN
The hallmark - progressive quantitative and qualitative deficiency of helper T cells

Mucosa

Submucosa

Langerhans cells

Cd4 lymphocytes and GALT

ECLIPSE

Dissemination
 OTHER MODES

transfusions, contaminated needles for injection drugs, sharp-object injuries, maternal-to

fetal transmission either intrapartum or perinatally, or sexual intercourse

Cleared from circulation

Lymphoid organs and spleen

Wider dissemination

ACUTE HIV SYNDROME

Viraemia ?
level of steady-state plasma viremia after ~1 year -------- slope of disease progression

high levels of viremia in acute HIV infection ------ higher likelihood of transmission of the
virus
chronicity

● Few thousands to few millions

● Though undetectable - low level replication ongoing
● Unlike usual viruses - no immunity
● Unlike hsv - clinical latency /=/ microbiological latency
● Unlike hcv/hbv - immune system is the target
Immune escape

● High rate of replication

● Inevitable mutations - quasi species
● Immune exhaustion
● downregulation of HLA class I molecules
● hypervariability in the primary sequence of the envelope
● extensive glycosylation of the envelope
● conformational masking of neutralizing epitopes
❖ broadly neutralizing antibodies -any help ?

❖ Reservoir - preintegration latency

❖ What if viraemia <50 copies

Clinical latency vs microbiological latency
Clinical latency is the period - viremia is in pace and cd4 count is falling,

Not disease latency

Long term survivors vs non progressors

❖ long-term nonprogressors- infected with HIV for ≥10 years their CD4+ T cell counts
were in the normal range without receiving cART [5–15%]
❖ “elite” controllers[ less than 1%] - extremely low levels of plasma viremia and
normal CD4+ T cell counts
Diagnosis
interval between infection and detection

➔ 22 days for antibody testing

➔ 16 days with p24 antigen testing
➔ 12 days with NAT
ELISA
extremely good screening test with a sensitivity of >99.5%

Generations

1. First generation – whole viral lysates

2. Second generation – recombinant antigen

3. Third generation – synthetic peptide

4. Fourth generation – antigen + antibody (Simultaneous detection of HIV antigen and

antibody) – HIV duo
per National HIV testing policy, two ELISA using different principles are required to
diagnose HIV infection
False positive results

• Autoimmune disorders

• Hematological malignancies (Plasmacytoma)

• Alcoholic hepatitis

• Connective tissue disorders

• Acute rheumatic fever

• Multiple pregnancies

• Multiple transfusions

• Post-vaccination including HIV vaccine

• Chronic renal failure

• Positive rapid plasma reagin test

• Technical errors, etc.

A HIV-infected individual treated early in the course of infection may revert to a negative
EIA. what does this mean?
False negative
• Window period (up to 3 months)
• Immunosuppressive therapy
• Replacement transfusion
• B-cell dysfunction
• Malignant disorder
• Late stage disease (immune collapse)
• Technical error
Western blot

● considered positive - antibodies exist to two of the three HIV proteins: p24, gp41,
and gp120/160
● the absence of the p31 band - false-positive test result
● positive / negative / “indeterminate.”
● Cross reactivity with p24 and/or p55.
WB positive
Organization Criteria

WHO 2 env with/without gag/pol

CDC Any two – p24, gp41, gp120/160

DuPont P24 and p31, and gp41 or gp120/160

p24 antigen capture assay - in acute HIV syndrome,

The ability to measure and monitor levels of HIV RNA in the plasma of patients with HIV
infection has been of extraordinary value in furthering our understanding of the
pathogenesis of HIV infection, in monitoring the response to cART, and in providing a
diagnostic tool
P24 ANTIGEN

The antigen test detects HIV free antigen (p24) in the serum.

This test is useful:

• During window period.

• To detect HIV infection in newborn because

diagnosis is difficult due to presence of maternal antibodies.

• During late disease when patient is symptomatic.

this test has a low sensitivity ?

Why is it important to know about HIV-2?

1. NNRTI’S do not work against HIV-2.

2. A patient doing well on ART, if super infected with HIV-2, will start failing
immunologically (CD4 count decreases), but viral load will stay undetectable (as viral
load detects HIV-1).
Quantitative HIV RNA estimation

★ reverse transcriptase PCR (RT-PCR; Amplicor)

★ branched DNA (bDNA; VERSANT)
★ transcription-mediated amplification (TMA; APTIMA)
★ nucleic acid sequence–based amplification (NASBA; NucliSENS).

One frequent consequence of a high degree of sensitivity is some loss of specificity, and
false-positive results have been reported with each of these techniques
RT-PCR and DNA-PCR ---- sequence analysis - study sequence diversity

microbial resistance to antiretroviral agents